Abolition of male sexual behaviors in mice lacking estrogen receptors α and β (αβERKO)

TLDR

The study aimed to assess the behavioral phenotype of mice lacking both estrogen receptor‑α and –β (αβERKO). The authors measured sexual and aggressive behaviors in these double‑knockout mice. AlphabetaERKO males showed complete loss of sexual behaviors and reduced aggression, whereas ER‑β single knockouts retained normal sexual activity and ER‑α knockouts exhibited only reduced aggression, indicating redundancy for mounting but ER‑α–specific control of offensive attacks.

Abstract

Male mice with a knockout of the estrogen receptor (ER)-alpha gene, a ligand-activated transcription factor, showed reduced levels of intromissions and no ejaculations whereas simple mounting behavior was not affected. In contrast, all components of sexual behaviors were intact in male mice lacking the novel ER-beta gene. Here we measure the extent of phenotype in mice that lack both ER-alpha and ER-beta genes (alphabetaERKO). alphabetaERKO male mice did not show any components of sexual behaviors, including simple mounting behavior. Nor did they show ultrasonic vocalizations during behavioral tests with receptive female mice. On the other hand, reduced aggressive behaviors of alphabetaERKO mice mimicked those of single knockout mice of ER-alpha gene (alphaERKO). They showed reduced levels of lunge and bite aggression, but rarely showed offensive attacks. Thus, either one of the ERs is sufficient for the expression of simple mounting in male mice, indicating a redundancy in function. Offensive attacks, on the other hand, depend specifically on the ER-alpha gene. Different patterns of natural behaviors require different patterns of functions by ER genes.